Activation of Proteases in Cerulein-Induced Pancreatitis

Yamaguchi, Hiroya; Kimura, Toshinari; Mimura, Kazuo; Nawata, Hajime

doi:10.1097/00006676-198910000-00007

Cited by 84 publications

(35 citation statements)

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“…A fraction of trypsinogen is prematurely autoactivated to trypsin within pancreatic acini under normal conditions; defective neutralization of this trypsin is the cause of hereditary pancreatitis (12). Trypsin is also prematurely activated when acinar cell function is impaired, such as in inflammation (10,29,30). Trypsin produced in these circumstances may leak into the interstitium from damaged acinar cells and cleave PAR-2 at the basal membrane of PDEC.…”

Section: Discussionmentioning

confidence: 99%

Trypsin activates pancreatic duct epithelial cell ion channels through proteinase-activated receptor-2

et al. 1999

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Section: Discussionmentioning

confidence: 99%

Trypsin activates pancreatic duct epithelial cell ion channels through proteinase-activated receptor-2

et al. 1999

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“…The premature activation of these proteolytic and lipolytic zymogens has been assigned a central role in the pathogenesis of acute pancreatitis (1). This concept of "autodigestion" is supported by the detection of activated digestive en-zymes within the pancreas in both clinical (2) and experimental forms of pancreatitis (3,4).…”

Section: Introductionmentioning

confidence: 99%

Intracellular activation of digestive zymogens in rat pancreatic acini. Stimulation by high doses of cholecystokinin.

Leach¹,

Modlin²,

Scheele³

et al. 1991

J. Clin. Invest.

190

121

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The mechanism by which digestive zymogens become activated during acute pancreatitis remains poorly understood. Given the ability for cholecystokinin (CCK) to induce pancreatitis in vivo, the effects of high dose CCK on preparations of isolated pancreatic acini were examined. Using an immunologic technique for the detection of zymogen activation, CCK was found to stimulate the conversion of procarboxypeptidase Al to a 35-kD form having the same net charge and electrophoretic mobility as purified recombinant carboxypeptidase Al. This enhanced conversion was proportional to the dose of CCK (maximal at 100 nM), and time dependent. CCK also produced changes in the electrophoretic mobility of procarboxypeptidase B and chymotrypsinogen 2 immunoreactivity, consistent with activation of these zymogens. These events were detectable only within acinar cell pellets and not in the incubation medium, suggesting an intracellular site of conversion. The conversion of procarboxypeptidase Al to its active form was inhibited by pretreatment with the weak base chloroquine (40MM) and the protonophore monensin (10 AM). This conversion was also inhibited by pretreatment with the serine protease inhibitor benzamidine (10 mM) but not the cysteine protease inhibitor E64 (100 MM). The results suggest that high dose CCK stimulates the intracellular activation of digestive zymogens within isolated pancreatic acini. This event appears to require an acidic subcellular compartment and serine protease activity. (J. Clin. Invest.

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“…ZG = Zymogengranules; CoV = condensing vacuoles; L = lysosome; RER = rough endoplasmic reticulum. lar activation of proteases does, in fact, occur during the initial phase of acute experimental pancreatitis [43][44][45],…”

Section: Early Intracellular Events In Acute Pancreatitismentioning

confidence: 99%

Pathophysiology of Acute Pancreatitis

Lerch¹,

Adler²

1994

Dig Surg

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The vast majority of patients with acute pancreatitis either have gallstones or drink too much alcohol. While little is known about the action of ethanol on the exocrine pancreas, the mechanisms involved in gallstone-induced pancreatitis have recently been elucidated to an extent that allows conclusions about the pathophysiology of pancreatitis. In the following review article we will discuss the clinical and experimental studies which have shaped our understanding of biliary pancreatitis. While most of the questions regarding the association of gallstones and pancreatitis appear to be resolved, the intracellular alterations which immediately follow these triggering events and ultimately lead to acinar cell necrosis are less well understood. These early pathophysiological changes within the pancreas have been the target of an intense research interest and the subject of sometimes equally passionate controversies. We will discuss the studies that have addressed the premature and intracellular activation of digestive enzymes in acute pancreatitis and review some of the current theories and arguments which attempt to confront this issue.

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Activation of Proteases in Cerulein-Induced Pancreatitis

Cited by 84 publications

References 0 publications

Trypsin activates pancreatic duct epithelial cell ion channels through proteinase-activated receptor-2

Trypsin activates pancreatic duct epithelial cell ion channels through proteinase-activated receptor-2

Intracellular activation of digestive zymogens in rat pancreatic acini. Stimulation by high doses of cholecystokinin.

Pathophysiology of Acute Pancreatitis

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